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Satoaki Matoba,1Ju-Gyeong Kang,1Willmar D. Patino,1Andrew Wragg,1Manfred Boehm,1Oksana Gavrilova,2Paula J. Hurley,3Fred Bunz,3Paul M. Hwang1*
The energy that sustains cancer cells is derived preferentiallyfrom glycolysis. This metabolic change, the Warburg effect,was one of the first alterations in cancer cells recognizedas conferring a survival advantage. Here, we show that p53,one of the most frequently mutated genes in cancers, modulatesthe balance between the utilization of respiratory and glycolyticpathways. We identify Synthesis of Cytochrome c Oxidase 2 (SCO2)as the downstream mediator of this effect in mice and humancancer cell lines. SCO2 is critical for regulating the cytochromec oxidase (COX) complex, the major site of oxygen utilizationin the eukaryotic cell. Disruption of the SCO2 gene in humancancer cells with wild-type p53 recapitulated the metabolicswitch toward glycolysis that is exhibited by p53-deficientcells. That SCO2 couples p53 to mitochondrial respiration providesa possible explanation for the Warburg effect and offers newclues as to how p53 might affect aging and metabolism.
1 Cardiology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA. 2 Diabetes Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA. 3 Department of Radiation Oncology and Molecular Radiation Sciences, The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins School of Medicine, Baltimore, MD 21231, USA.
* To whom correspondence should be addressed. E-mail: hwangp{at}mail.nih.gov
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